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Abstract BACKGROUND More than a million Americans harbor a cerebral cavernous angioma (CA), and those who suffer a prior symptomatic hemorrhage have an exceptionally high rebleeding risk. Preclinical studies show that atorvastatin blunts CA lesion development and hemorrhage through inhibiting RhoA kinase (ROCK), suggesting it may confer a therapeutic benefit. OBJECTIVE To evaluate whether atorvastatin produces a difference compared to placebo in lesional iron deposition as assessed by quantitative susceptibility mapping (QSM) on magnetic resonance imaging in CAs that have demonstrated a symptomatic hemorrhage in the prior year. Secondary aims shall assess effects on vascular permeability, ROCK activity in peripheral leukocytes, signal effects on clinical outcomes, adverse events, and prespecified subgroups. METHODS The phase I/IIa placebo-controlled, double-blinded, single-site clinical trial aims to enroll 80 subjects randomized 1-1 to atorvastatin (starting dose 80 mg PO daily) or placebo. Dosing shall continue for 24-mo or until reaching a safety endpoint. EXPECTED OUTCOMES The trial is powered to detect an absolute difference of 20% in the mean percent change in lesional QSM per year (2-tailed, power 0.9, alpha 0.05). A decrease in QSM change would be a signal of potential benefit, and an increase would signal a safety concern with the drug. DISCUSSION With firm mechanistic rationale, rigorous preclinical discoveries, and biomarker validations, the trial shall explore a proof of concept effect of a widely used repurposed drug in stabilizing CAs after a symptomatic hemorrhage. This will be the first clinical trial of a drug aimed at altering rebleeding in CA.

To explore the advantages and disadvantages of 3D Slicer reconstruction and 3D printing localization combined with transcranial neuroendoscope in the surgical treatment of deep cerebral micro cavernous hemangiomas. Method The clinical data of patients with deep cerebral micro cavernous hemangiomas treated by our hospital from June 2022 to February 2023 using 3D Slicer reconstruction and 3D printing localization technology combined with transcranial endoscopic surgery were retrospectively analyzed. A total of 5 cases with complete data were collected, including 2 males and 3 females, aged 9–59 years. All 5 patients had deep supratentorial cavernous hemangiomas with a diameter of less than 1.5 cm, and had clinical symptoms such as headache or epilepsy, and had been diagnosed by CT or MRI. Repeated bleeding from small cavernous hemangiomas in the deep brain can lead to clinical symptoms such as recurrent headache and epilepsy, and is required surgical treatment. However, cavernous hemangiomas often have smaller lesions and are difficult to locate in the deep part. Without neuronavigation, surgery can become extremely difficult. Our team’s newly developed 3D Slicer reconstruction and 3D printing localization technology which could provide new options for surgical treatment of small cavernous hemangiomas or other small lesions in the deep brain, but its accuracy and safety still need to be verified by further clinical research.

Abstract BACKGROUND Cerebral cavernous angioma (CA) is a capillary microangiopathy predisposing more than a million Americans to premature risk of brain hemorrhage. CA with recent symptomatic hemorrhage (SH), most likely to re-bleed with serious clinical sequelae, is the primary focus of therapeutic development. Signaling aberrations in CA include proliferative dysangiogenesis, blood-brain barrier hyperpermeability, inflammatory/immune processes, and anticoagulant vascular domain. Plasma levels of molecules reflecting these mechanisms and measures of vascular permeability and iron deposition on magnetic resonance imaging are biomarkers that have been correlated with CA hemorrhage. OBJECTIVE To optimize these biomarkers to accurately diagnose cavernous angioma with symptomatic hemorrhage (CASH), prognosticate the risk of future SH, and monitor cases after a bleed and in response to therapy. METHODS Additional candidate biomarkers, emerging from ongoing mechanistic and differential transcriptome studies, would further enhance the sensitivity and specificity of diagnosis and prediction of CASH. Integrative combinations of levels of plasma proteins and characteristic micro-ribonucleic acids may further strengthen biomarker associations. We will deploy advanced statistical and machine learning approaches for the integration of novel candidate biomarkers, rejecting noncorrelated candidates, and determining the best clustering and weighing of combined biomarker contributions. EXPECTED OUTCOMES With the expertise of leading CA researchers, this project anticipates the development of future blood tests for the diagnosis and prediction of CASH to clinically advance towards precision medicine. DISCUSSION The project tests a novel integrational approach of biomarker development in a mechanistically defined cerebrovascular disease with a relevant context of use, with an approach applicable to other neurological diseases with similar pathobiologic features. Graphical Abstract Graphical Abstract

An 8-year-old boy presenting with left-angle paralysis, tremor in upper and lower extremities, and diplopia was diagnosed with hemorrhage from a mesencephalic cavernous hemangioma. He underwent hemangiomectomy through the occipital transtentorial approach 4 weeks post-hemorrhage, after which Holmes tremor (HT) markedly reduced. A year later, hemangioma has not recurred; he is now independent in his daily activities. Early intervention in the subacute stage allows for the complete removal of brainstem cavernomas (BSCs), with minimal risk of complications or sequelae. Proper timing and surgical approach for BSCs can prevent re-bleeding and improve HT after an initial hemorrhage, without any lasting negative consequences.

Background Cavernous hemangioma is a congenital insidious disease that can occur in any part of the central nervous system. In clinical practice, cavernous hemangioma is mostly found in the brain and rarely in the spinal cord. Case summary This study describes a case of a 34-year-old Chinese man of Han ethnicity with lumbar intramedullary cavernous hemangioma. On admission, lumbar intramedullary hemorrhage was observed in the patient, as well as a spindle-shaped hematoma sign was detected on the spinal magnetic resonance imaging. We suspected that the spinal hemorrhage could be associated with spinal cord cavernous hemangioma. The patient was started on dehydration and glucocorticoid therapy of mannitol on the day of admission and was diagnosed with cavernous hemangioma on the basis of his magnetic resonance imaging presentation and spinal cord histopathology results. However, there was no significant improvement in clinical manifestations following conservative treatment. It was exciting that the patient’s condition improved after the surgical removal of hematomas. Conclusion Clinicians should consider lumbar intramedullary cavernous hemangioma in the differential diagnosis of early spinal cord hemorrhage with a spindle-shaped hematoma sign on the spinal magnetic resonance imaging.

Background Hepatic hemangiomas (HHs) are benign liver lesions often discovered incidentally on imaging for various unrelated pathologies. We herein review the etiology, classification, diagnostic imaging, and management of HHs. Methods A comprehensive systematic review was performed utilizing MEDLINE/PubMed and Web of Science databases, with the end of search date being March 1, 2022, regarding HH diagnosis, imaging, and management. Results HHs can be broadly classified as capillary hemangiomas or cavernous hemangiomas. While the exact pathophysiology related to the development of HHs remains largely unknown, hormone exposure has been postulated to cause HH growth. HHs appear homogenously hyperechoic on US with distinct margins and posterior acoustic enhancement. While cavernous hemangiomas appear as well-defined hypodense lesions on pre-contrast CT images with the same density as the vasculature, one of the most reliable imaging features for diagnosing cavernous hemangiomas is high signal intensity on T2 weighted images. While most HHs are asymptomatic, some patients can present with pain or compressive symptoms with bleeding/rupture being very rare. Kasabach-Merritt syndrome is a rare but life-threatening condition associated with thrombocytopenia and microangiopathic hemolytic anemia. When HHs are symptomatic or in the setting of Kasabach Merritt syndrome, surgery is indicated. Enucleation is an attractive surgical option for HH as it spares normal liver tissue. Most patients experience symptom relief following surgical resection. Conclusion HHs are very common benign liver lesions. High-quality imaging is imperative to distinguish HHs from other liver lesions. Surgery is generally reserved for patients who present with symptoms such as pain, obstruction, or rarely Kasabach-Merritt syndrome. Surgery can involve either formal resection or, in most instances, simple enucleation. Patients generally have good outcomes following surgery with resolution of their symptoms.

The pons is the most frequent local for brain stem cavernoma.1 Repeated hemorrhage of brainstem cavernoma is associated with significant and accumulative neurological deficits and thus requires treatment. According to the Swedish Karolinska’s group of radiosurgery, ”it could not be concluded whether GKRS affects the natural course of a CM. The incidence of radiation-induced complications was approximately seven times higher than that expected.”2 Thus, microsurgical removal has become the mainstay of treatment. In our experience, the following details assist in obtaining favorable outcomes and avoiding postoperative complications3,4: (a) the entry into the cavernoma based on thorough knowledge of the microanatomy; (b) the detailed study of the images and the presentation of the cavernoma on or near the brain stem surface; (c) the resection of the live cavernous hemangioma and not the mere removal of the multiple aged organized hematomas; (d) the preservation of the associated venous angioma; (e) the direct and shortest access to the lesion provided by a skull base approach; and (f) the use of the available technology, such as intraoperative neuromonitoring and neuroimaging. We present the case of a 54-yr-old male with recent deterioration in year 2001, past repetitive episodes of gait imbalance, and speech difficulty over a 7-yr period from known pontine cavernoma. The anterior petrosal approach provided superb and direct exposure to the entry at the lateral pons and the cavernoma was totally removed with preservation of the venous angioma. His preoperative neurological deficit rapidly recovered. Patient consented to the procedure and photography. Images at 3:15 from Kadri et al, The anatomical basis for surgical presercation of temporal muscle. J Neurosurg. 2004;100:517-522, used with permission from JNSPG. Image at 3:27 from Al-Mefty O, Operative Atlas of Meningiomas, © LWW, 1997, with permission.

Background Cerebral cavernous malformations (CCMs) are known to be vascular anomalies with low perfusion because of being angiographically occult. We attempted direct visualization of blood flow within CCMs and orbital cavernous angiomas (CAs), and analyzed flow dynamics using indocyanine green videoangiography (ICG-VAG). Methods This series included seven CCMs and two orbital CAs. ICG-VAG was performed to visualize blood flow of the lesions before resection. Time to peak of staining was evaluated by reviewing recorded ICG-VAG. Results In five of seven CCMs, stain was identified. CCMs were seen as avascular areas in both arterial and venous phases, and were stained gradually. Stain was maximized late after venous phase. The orbital CAs were also stained lately, but more intensely than CCMs. Conclusions The present study directly demonstrated slow and low perfusion within CCM and orbital CA using ICG-VAG. On the basis of characteristic flow dynamics of CCMs, intraoperative ICG-VAG provides useful information in microsurgical resection.

A woman in her early 50s presented with an 8-month history of bilateral lower limb weakness and a 3-month history of unsteady gait. Imaging revealed a dumbbell-shaped mass near T1-T3, initially diagnosed as a schwannoma. Intraoperatively, a highly vascular dark red tumor was discovered, and only partial resection was performed due to bleeding risk. Pathology confirmed an epidural cavernous hemangioma. Symptoms had significantly improved at the 2-month follow-up without recurrence. This case highlights the importance of comprehensive preoperative imaging to prevent misdiagnosis and optimize surgical planning for atypically located tumors.